Acute STEMI Rx.pptx

ACUTE ST ELEVATION MI:
Current Standard of Care
DR SHARAT M VIJAPUR
CONSULTANT INTERVENTIONAL CARDIOLOGIST
SECURE HOSPITAL HUBLI

Revised Definition of Myocardial Infarction

Classification of Myocardial Infarction

PREHOSPITAL AND
INITIAL MANAGEMENT

Major components of time delay between onset of
infarction and restoration of flow in the IRA

B
C
A
Extent of
Myocardial Salvage
Mortality
Reduction
(%)
D
100
80
60
40
20
0
0 4 8 12 16 20 24
Time From Symptom Onset to Reperfusion Therapy, h
Critical Time-dependent Period
Goal: Myocardial Salvage
Time-independent Period
Goal: Open Infarct-Related Artery
Gersh BJ, et al. JAMA. 2005;293:979.
1. Time is Myocardium
2. Infarct Size is Outcome

Reperfusion Therapy
Efficacy and Time Frame
Total occlusion

Role of Pre-hospital fibrinolysis
Not cost effective.
No individual trials (including CAPTIM) showed a
significant improvement in mortality.
A meta-analysis of all available trials  a 17% reduction in
mortality.
Reasonable if
 Physicians are present in the ambulance
 A well organised EMS system with full-time paramedics, capability for
obtaining and transmitting 12 lead ECG from the field, and online
medical command to authorize pre-hospital fibrinolysis

Management in the Emergency Department
Targeted medical history and physical exam.
Differential diagnosis.
Lab exam: CK MB, Troponins, others
Diagnostic testing : ECG, ECHO

ECG in STEMI
Definitive diagnosis:
ST elevation > 1 mm in > 2 contiguous leads,
often with reciprocal ST depression in
contralateral leads.
In leads V2 – V3, 2 mm of ST elevation in men and 1.5 mm in women is
reqd for accurate diagnosis.

ECG in STEMI (contd)
New LBBB with ischemic symptoms may
indicate a large acute AWMI, involving
proximal LAD
In the absence of an old ECG or in the
presence of LBBB at baseline, the
diagnosis of acute MI can be made in the
presence of LBBB with > 90% specificity
on the basis of the following criteria:

RISK STRATIFICATION
Five simple baseline parameters have
been reported to account for > 90% of the
prognostic information for 30 day mortality.
These parameters in descending order of
importance are:
• Age
• Systolic BP
• Killip classification
• Heart rate
• Location of MI

30 day mortality based on Killip class (GUSTO I)
Class Characteristics Patients Mortality rate
I No evidence of CHF 85% 5.1%
II Rales, ↑ JVP, or S3 13% 13.6%
III Pulmonary edema 1% 32.2%
IV Cardiogenic shock 1% 57.8%

Initial medical therapies in the ED
Aspirin: To be chewed; 162 mg -to 325 mg .
Clopidogrel 300mg
Unfractionated heparin v/s LMWH
STATINS
S/L NTG : 0.4 mg every 5 minutes, for a total of 3 doses.
Intravenous (IV) nitroglycerin is then indicated for
 relief of ongoing ischemic discomfort,
 control of hypertension, or
 management of pulmonary congestion (Class I; LOE, C).
Nitrates should not be administered to patients with
 SBP < 90 mm Hg or SBP ≥ 30 mm Hg below baseline,
 severe bradycardia (<50 beats/min), tachycardia (>100 beats/min), or
 suspected RV infarction (Class III; LOE, C).

Analgesia: Morphine sulfate (2 to 4 mg IV, with increments of 2 to 8 mg IV
repeated at 5- to 15-minute intervals) is the analgesic of choice for management
of pain associated with STEMI (Class I; LOE, C).
Beta blockers: Oral beta blocker therapy should be initiated for patients who do
not have any of the following:
(1) signs of heart failure;
(2) 2nd and 3rd degree AV block;
(3) cardiogenic shock; or
(4) other relative contraindications (e.g., PR interval > 0.24 second, HR < 60/min,
SBP< 100, or reactive airway disease) (Class I; LOE, B).
Supplemental oxygen:
1.To patients with arterial oxygen desaturation (i.e., Sao2 < 90%) (Class I; LOE, B),
2. To all patients with uncomplicated STEMI during the first 6 hours (Class IIa; LOE, C).

Reperfusion
• Given the current literature, it is not possible to say
definitively that a particular reperfusion approach is
superior for all pts, in all clinical settings, at all times of
day
• The main point is that some type of reperfusion therapy
should be selected for all appropriate pts with suspected
STEMI
• The appropriate & timely use of some reperfusion
therapy is likely more important than the choice of
therapy

Reperfusion
The medical system goal is to facilitate rapid recognition
and treatment of patients with STEMI such that door-to-
needle (or medical contact–to-needle) time for initiation
of fibrinolytic therapy can be achieved within 30
minutes or that door-to-balloon (or medical contact–to-
balloon) time for PCI can be kept within 90 minutes.

Symptom
Recognition
Call to
Medical
System
ED Cath Lab
PreHospital
Delay in Initiation of Reperfusion
Therapy
Increasing Loss of Myocytes
Treatment Delayed is Treatment Denied

Time to Reperfusion
• The dependence of myocardial salvage on time to treatment pertains to
patients treated with fibrinolysis or PCI.
• Each 30-minute delay from symptom onset to PCI increases the relative
risk (RR) of 1-year mortality by 8%.

Reperfusion Options for STEMI Patients
Step One: Assess Time and Risk.
Time Since
Symptom
Onset
Time Required
for Transport to
a Skilled PCI
Lab
Risk of STEMI Risk of
Fibrinolysis

Fibrinolysis generally preferred
 Early presentation ( ≤ 3 hours from symptom
onset and delay to invasive strategy)
 Invasive strategy not an option
 Cath lab occupied or not available
 Vascular access difficulties
 No access to skilled PCI lab
 Delay to invasive strategy
 Prolonged transport
 Door-to-balloon more than 90 minutes
 > 1 hour vs fibrinolysis (fibrin-specific agent) now
Step 2: Select Reperfusion Treatment.
If presentation is < 3 hours and there is no delay to an invasive
strategy, there is no preference for either strategy.

Invasive strategy generally preferred
 Skilled PCI lab available
 Door-to-balloon < 90 minutes
• High Risk from STEMI
 Cardiogenic shock, Killip class ≥ 3
 Contraindications to fibrinolysis, including
increased risk of bleeding and ICH
 Late presentation
 > 3 hours from symptom onset
 Diagnosis of STEMI is in doubt
Step 2: Select Reperfusion Treatment.

Benefit of lysis- FTT
collaborative
study
The absolute mortality reduction
was
1. 30 per 1000 patients presenting
within 0 - 6 hours
2. 20 per 1000 patients presenting
between 7 and 12 hours.
3. Beyond 12 hours, the benefit
was uncertain

Fibrinolysis
If pharmacologic reperfusion is selected,
fibrinolytic therapy should be administered to STEMI patients with
symptom onset within the prior 12 hours (Class I; LOE, A).
In the absence of contraindications, it is reasonable to administer
fibrinolytic therapy to patients with symptoms of STEMI beginning within
the prior 12 to 24 hours who have continuing ischemic symptoms and
electrocardiographic evidence of STEMI (Class IIa; LOE, C).
Fibrinolytic therapy should not be administered to
 asymptomatic patients whose initial symptoms of STEMI began more than
24 hours earlier (Class III; LOE, C)
 nor to patients whose 12-lead ECG shows only ST-segment depression,
except if a true posterior myocardial infarction (MI) is suspected (Class III;
LOE, A).

Comparison of Fibrinolytic Agents

Thrombolytic regimens for
acute ST elevation myocardial infarction

Choice of agent
No particular recommendation.
• Patients presenting within 4 hrs of symptoms
 In patients with high risk of death: 3rd generation fibrinolytics.
 In patients with low risk of mortaliy (e.g., a young patient with a small IWMI)
and in patients with high risk of ICH (e.g., acute hypertension):
Both STK and 3rd generation fibrinolytics are equivalent.
• Patients presenting between 4 and 12 hrs after symptom onset
 Both STK and 3rd generation fibrinolytics are equivalent.

Late Fibrinolysis
• LATE and EMERAS  No mortality benefit for fibrinolysis
between 12 and 24 hrs.
• Reasonable in patients with persistent symptoms and ST-
segment elevation beyond 12 hrs.
• Preferable to restrict late fibrinolytic administration to
patients < 65yrs with ongoing ischemia, especially those
with large anterior infarctions.

Assessment of Reperfusion
It is reasonable to monitor the pattern of ST elevation,
cardiac rhythm and clinical symptoms over the 60 to 180
minutes after initiation of fibrinolytic therapy.
Noninvasive findings suggestive of reperfusion include:
 Relief of symptoms
 Maintenance and restoration of hemodynamic and/or
electrical instability
 Reduction of ≥ 50% of the initial ST-segment elevation
pattern on follow-up ECG 60 to 90 minutes after
initiation of therapy.

Contraindications and Cautions
for Fibrinolysis in STEMI
Absolute Contraindications
Haemorrhagic stroke or stroke of unknown origin at any
time
• Ischemic stroke in preceding 6 months
• Central nervous system trauma or neoplasms
• Recent major trauma / surgery / head injury within
preceding 3 months
• Gastrointestinal bleeding within the last month
• Known bleeding disorder • Aortic dissection

Primary Angioplasty
• Primary angioplasty was compared with thrombolysis for patients with
AMI in 23 randomized trials involving more than 7500 patients.
• A meta-analysis of these trials showed that compared with fibrinolysis,
PPCI resulted in
 25% reducation in death,
 64% reduction in reinfarction,
 95% reduction in ICH, and
 53% reduction in stroke.
Keeley EC et al, Primary angioplasty versus intravenous thrombolytic
therapy for acute myocardial infarction: a quantitative review of 23
randomized trials. Lancet. 2003, 361: 13-20.

Primary PCI for STEMI:
General Considerations
 Patient with STEMI (including posterior MI) or MI with
new or presumably new LBBB
 PCI of infarct artery within 12 hours of symptom onset
 Balloon inflation within 90 minutes of presentation
 Skilled personnel available (individual performs > 75
procedures per year)
 Appropriate lab environment (lab performs > 200
PCIs/year of which at least 36 are primary PCI for
STEMI)

Specific Considerations
 Medical contact–to-balloon or door-to-balloon
should be within 90 minutes.
 PCI preferred if > 3 hours from symptom onset.
 Primary PCI should be performed in patients
with severe congestive heart failure (CHF)
and/or pulmonary edema (Killip class 3) and
onset of symptoms within 12 hours.

Specific Considerations
It is reasonable to perform primary PCI for patients with
onset of symptoms within the prior 12 to 24 hours and 1 or
more of the following:
a. Severe CHF
b. Hemodynamic or electrical instability
c. Persistent ischemic symptoms

Rescue PCI
Class I
A strategy of coronary angiography with intent to perform
PCI (or emergency CABG) is recommended for patients
who have received fibrinolytic therapy and have any of
the following:
• Cardiogenic shock in patients younger than 75 years who
are suitable candidates for revascularization
• Severe congestive heart failure and/or pulmonary edema
(Killip Class III)
• Hemodynamically compromising ventricular arrhythmias

PCI after successful fibrinolysis or for
patients not undergoing primary reperfusion
Class I
In patients whose anatomy is suitable, PCI should
be performed when there is
• objective evidence of recurrent MI.
• moderate or severe spontaneous or provokable
myocardial ischemia during recovery from
STEMI.
• shock or hemodynamic instability.

48
Recommendations for triage and
transfer for Percutaneous
Coronary Intervention for Patients
with STEMI

49
Recommendations for Triage and
Transfer for PCI (for STEMI) (cont.)
NEW
Recommendation
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III
It is reasonable to transfer high
risk patients who receive fibrinolytic
therapy as primary reperfusion
therapy at a non-PCI capable facility
to a PCI-capable facility as soon as
possible where either PCI can be
performed when needed or as a
pharmacoinvasive strategy.

50
Recommendations for Triage and
Transfer for PCI (for STEMI) (cont.)
NEW
Recommendation
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III
Consideration should be given
to initiating a preparatory
antithrombotic (anticoagulant
plus antiplatelet) regimen prior
to and during patient transfer
to the catheterization
laboratory.

74
Recommendations for the Use of
Glycoprotein IIb/IIIa Receptor
Antagonists in STEMI

75
It is reasonable to start treatment with
glycoprotein IIb/IIIa receptor antagonists at the
time of primary PCI (with or without stenting) in
selected patients with STEMI:
abciximab
tirofiban and eptifibatide
Use of Glycoprotein IIb/IIIa Receptor
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III
Modified
Recommendation

76
Use of Glycoprotein IIb/IIIa Receptor
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III
The usefulness of glycoprotein IIb/IIIa receptor
antagonists (as part of a preparatory
pharmacologic strategy for patients with STEMI
prior to arrival in the cardiac catheterization
laboratory for angiography and PCI) is
uncertain.
Modified
Recommendation

Pathway: Triage and Transfer for PCI (in STEMI)
77
2009 STEMI Focused
Update. Appendix 5
STEMI patient who is a
candidate for reperfusion
Initially seen at a PCI
capable facility
Initially seen at a
non-PCI
capable facility
Send to Cath Lab for
primary PCI
(Class I, LOE:A)
Transfer for primary
PCI
(Class I, LOE:A)
Initial Treatment
with fibrinolytic
therapy
(Class 1, LOE:A)
Prep antithrombotic (anticoagulant
plus antiplatelet) regimen
Diagnostic angio
Medical
therapy only
PCI CABG
NOT HIGH RISK
Transfer to a PCI
facility may be
considered
(Class IIb,
LOE:C),
especially if
ischemic
symptoms
persist and
failure to
reperfuse is
suspected
HIGH RISK
Transfer to a PCI
facility is
reasonable for
early diagnostic
angio & possible
PCI or CABG
(Class IIa,
LOE:B),
High-risk
patients as
defined by 2007
STEMI Focused
Update should
undergo cath
(Class 1: LOE B)
At PCI
facility,
evaluate
for timing
of
diagnostic
angio

CONCLUSION
TIME IS MUSCLE-
ALL EFFORTS SHOULD BE MADE TO
GIVE SOME FORM OF REPERFUSION
THERAPY AS EARLY AS POSSIBLE

CONCLUSION
1. Thrombolytic therapy is beneficial, easily
accessible and affordable
2. When transfer delay is a problem,
thrombolysis is a good option. In such
situations, how quickly the reperfusion
therapy is delivered is more important than
which reperfusion therapy is offered.
3. Primary PCI has constraints in terms of
cost, availability, accessibility and expertise
while at the same time delivering better
patient outcomes.

81
FINESSE: Study design
Ellis et al. N Eng J Med. 2008;358:2205-2217.
Treatment
Pre-PCI treatment with ½ -dose lytic plus
abciximab, pre-PCI abciximab alone, and
abciximab at time of PCI
Inclusion
Suspected acute MI (ST change or LBBB)
within 6 h of symptom onset
Exclusion
Low risk (<60 yo, localized inferior infarct)
high risk for bleeding
1° OUTCOMES
Death, VF after 48 hours, shock,
CHF within 90 days

82
Primary, secondary, and bleeding end
points in FINESSE
End point Primary
PCI (%)
Abciximab-
facilitated
(%)
Combination
(abciximab/
reteplase)-
facilitated (%)
p, combination-
facilitated vs
primary PCI
p,
combination-
facilitated vs
abciximab-
facilitated
Primary end point*
at 90 days
10.7 10.5 9.8 NS NS
>70% ST segment
resolution within
60–90 min
31.0 33.1 43.9 0.003 0.01
TIMI major or
minor bleeding
through discharge
or day 7
6.9 10.1 14.5 <0.001 0.008
End point Primary
PCI (%)
Abciximab-
facilitated
(%)
Combination
(abciximab/
reteplase)-
facilitated (%)
p, combination-
facilitated vs
primary PCI
p,
combination-
facilitated vs
abciximab-
facilitated
Primary end point*
at 90 days
10.7 10.5 9.8 NS NS
>70% ST segment
resolution within
60–90 min
31.0 33.1 43.9 0.003 0.01
TIMI major or
minor bleeding
through discharge
or day 7
6.9 10.1 14.5 <0.001 0.008
*All-cause mortality; rehospitalization or emergency department treatment for CHF; resuscitated
ventricular fibrillation occurring >48 hours after randomization; cardiogenic shock
Ellis et al. N Eng J Med. 2008;358:2205-2217

83
OnTIME 2: Study design
Acute myocardial infarction
diagnosed in ambulance or referral center
ASA+600 mg Clopidogrel
Angiogram
Tirofiban *
Placebo
Transportation
PCI centre
Angiogram
Tirofiban
provisional
Tirofiban
cont’d
PCI
van’t Hof et al. Lancet 2008;372:537-46.

84
OnTIME 2: endpoints
Primary
• Residual ST segment deviation (>3mm) 1 hour after
PCI
Key Clinical Secondary
• Combined occurrence of death, recurrent MI, urgent
TVR or thrombotic bailout at 30 days follow-up
• Safety (major bleeding)
• Death at 1 year follow-up

85
On-TIME 2: Results
van’t Hof et al. Lancet 2008;372:537-46
Residual ST Deviation after PCI
p=0.003 3.6± 4.6mm 4.8± 6.3mm

86
On-TIME 2: Results
van’t Hof et al. Lancet 2008;372:537-46.
Event-free Survival at 30 days
Clinical outcome Placebo tirofiban P-value
Death/recurrent MI
or urgent TVR
39/477
(8.2%)
33/473
(7.0%)
0.485

87
BRAVE 3: Study design
Mehilli et al. Circ. 2009;119:1933-1940
TREATMENT: pre-PCI treatment with clopidogrel
(600 mg), followed by abciximab
vs. placebo
INCLUSION: suspected acute MI (ST change or LBBB)
within 24 h of symptom onset
EXCLUSION: high risk for bleeding, prior
stroke,shock,
trauma, thrombolytics, hypertension,
relevant hematologic deviations
1° OUTCOMES: infarct size, death, stroke, urgent
revascularization of affected artery

88
Effects of Abciximab
Mehilli et al. Circ. 2009;119:1933-1940
No significant
difference in infarct size
or major bleeding
P= 0.47
P= 0.40

89
Recommendations for the
use of Thienopyridines

90
Recommendations for the use of
Thienopyridines
A loading dose of thienopyridine is recommended for
STEMI patients for whom PCI is planned. Regimens should
be one of the following:
MODIFIED
Recommendation
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III
Clopidogrel at least 300 mg to 600mg† should
be given as early as possible before or at the
time of primary or non-primary PCI.

91
Thienopyridines
Prasugrel 60 mg should be given as
soon as possible for primary PCI.
MODIFIED
Recommendation
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III

92
TRITON-TIMI 38:
Study Design
Double-blind
ACS (STEMI or UA/NSTEMI) & Planned PCI
ASA
PRASUGREL
60 mg LD/ 10 mg MD
CLOPIDOGREL
300 mg LD/ 75 mg MD
1o endpoint: CV death, MI, Stroke
2o endpoints: CV death, MI, Stroke, Rehosp-Rec Isch
CV death, MI, UTVR
Stent Thrombosis (ARC definite/prob.)
Safety endpoints: TIMI major bleeds, Life-threatening bleeds
Key Substudies: Pharmacokinetic, Genomic
Median duration of therapy - 12 months
N= 13,600
Wiviott SD et al AHJ 152: 627,2006
Adapted with permission from E.Antman

93
B
OVERALL
No GPI
GPI
DES
BMS
DM
No DM
>75
65-74
<65
Female
Male
STEMI
UA/NSTEMI
0.5 1 2
Prasugrel Better Clopidogrel Better
HR
Age
Reduction in risk (%)
18
21
12
25
14
6
14
30
20
18
21
16
19
21
Pinter = NS
CV Death, MI, Stroke
Major Subgroups
CrCl > 60
CrCl < 60 14
20
Wiviott SD et al NEJM 357: 2001, 2007
TRITON TIMI-38

94
0
2
4
6
8
0 1 2 3
1
0
306090 180 270 360 450
HR 0.82
P=0.01
HR 0.80
P=0.003
5.6
4.7
6.9
5.6
Days
Primary
Endpoint
(%)
Prasugrel
Clopidogrel
Prasugrel
Clopidogrel
Loading Dose Maintenance Dose
Timing of Benefit
(Landmark Analysis - 3 days)
Adapted with permission from Antman EM JACC 2008.
TRITON TIMI-38

95
Diabetic Subgroup
0
2
4
6
8
10
12
14
16
18
0 30 60 90 180 270 360 450
HR 0.70
P<0.001
Days
Endpoint
(%)
CV Death / MI / Stroke
TIMI Major
NonCABG Bleeds
NNT = 21
N=3146
17.0
12.2
Prasugrel
Clopidogrel
Prasugrel
Clopidogrel 2.6
2.5
Wiviott SD et al Circulation 2008.Adapted with
permission from Antman EM.
TRITON TIMI-38

96
0
5
10
15
0 30 60 90 180 270 360 450
Percent
(%)
Days From Randomization
9.5%
6.5%
HR 0.68
(0.54-0.87)
P=0.002
12.4%
10.0%
HR 0.79
(0.65-0.97)
P=0.02
Clopidogrel
Prasugrel
NNT = 42
CV Death / MI / Stroke
TIMI Major
NonCABG Bleeds
Clopidogrel
Prasugrel 2.4
2.1
STEMI Cohort
N=3534
Montalescot et al Lancet 2008.Adapted with
permission from Antman EM.
TRITON TIMI-38

97
Stent Thrombosis
(ARC Definite + Probable)
0
1
2
3
0 30 60 90 180 270 360 450
HR 0.48
P <0.0001
Prasugrel
Clopidogrel
2.4
(142)
NNT= 77
1.1
(68)
Days
Endpoint
(%)
Any Stent at Index PCI
N= 12,844
Adapted with permission from Wiviott SD et al
Lancet 2008
Significant reductions both with BMS, DES
Significant reductions in early and late stent thromboses
TRITON TIMI-38

98
1.8
0.9 0.9
0.1
0.3
2.4
1.4
1.1
0.4 0.3
0
2
4
TIMI Major
Bleeds
Life
Threatening
Nonfatal Fatal ICH
%
Events
ARD 0.6%
HR 1.32
P=0.03
NNH=167
Clopidogrel
Prasugrel
ARD 0.5%
HR 1.52
P=0.01
ARD 0.2%
P=0.23
ARD 0%
P=0.74
ARD 0.3%
P=0.002
ICH in Pts w
Prior Stroke/TIA
(N=518)
Clop 0 (0) %
Pras 6 (2.3)%
(P=0.02)
Wiviott SD et al NEJM 357: 2001, 2007.
Adapted with permission from Antman EM.
TRITON TIMI-38: Bleeding Events
Safety Cohort (N=13,457)

TRITON-TIMI 38: Results summary
Treatment with prasugrel was associated with a 21% relative reduction in
the risk cardiovascular death, myocardial infarction, or stroke during 15
months of follow-up.
Major bleeding was increased with prasugrel in the trial overall, but not
among patients with ST-elevation myocardial infarction.

100
Thienopyridines
For STEMI patients undergoing non-primary PCI, the
following regimens are recommended:
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III a. …and has been given clopidogrel, it should be
continued as the thienopyridine of choice.
b. …without a thienopyridine, a loading dose of 300-600‡
mg of clopidogrel should be given as the
thienopyridine of choice.
If the patient did not receive fibrinolytic therapy…
c. …either a loading dose of 300-600 mg of clopidogrel
should be given or, once the coronary anatomy is
known and PCI is planned, a loading dose of 60 mg of
prasugrel should be given promptly and no later than 1
hour after the PCI.
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
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IIa
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IIb III
III
III
If the patient has received fibrinolytic therapy…
MODIFIED
Rec

101
Thienopyridines
The duration of thienopyridine therapy
should be as follows:
MODIFIED
Recommendation
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III
III
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IIa
IIa
IIa IIb
IIb
IIb III
III
III
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IIa
IIa IIb
IIb
IIb III
III
III
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IIa IIb
IIb
IIb III
III
III
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IIa
IIa IIb
IIb
IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III a. In patients receiving a stent (BMS or DES)
during PCI for ACS, clopidogrel 75 mg daily†
or prasugrel 10 mg§ daily should be given
for at least 12 months;
b. If the risk of morbidity from bleeding
outweighs the anticipated benefit afforded
by thienopyridine therapy, earlier
discontinuation should be considered.

102
Thienopyridines
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IIa
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IIb III
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III
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III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III
In patients taking a thienopyridine in whom coronary
artery bypass surgery (CABG) is planned and can be
delayed, it is recommended that the drug be discontinued
to allow for dissipation of the antiplatelet effect.
The period of withdrawal should be at least 5 days in
patients receiving clopidogrel
and at least 7 days in patients receiving prasugrel,
… unless the need for revascularization and/or the net
benefit of the thienopyridine outweighs the potential risks
of excess bleeding.
MODIFIED
Recommendation (prasugrel added)
I
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III
III
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III
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IIa
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IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
I
I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
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I IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
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IIa
IIa IIb
IIb
IIb III
III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III
I
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I IIa
IIa
IIa IIb
IIb
IIb III
III
III
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IIa
IIa IIb
IIb
IIb III
III
III
I
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III
III
IIa
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IIa IIb
IIb
IIb III
III
III

103
Thienopyridines
MODIFIED
Recommendation
Continuation of clopidogrel or
prasugrel beyond 15 months may
be considered in patients
undergoing drug-eluting stent
placement
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IIa
IIa IIb
IIb
IIb III
III
III
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III
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III
III

104
Thienopyridines
NEW
Recommendation
In STEMI patients with a prior
history of stroke and transient
ischemic attack for whom primary
PCI is planned, prasugrel is not
recommended as part of a dual
antiplatelet therapy regimen
I
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IIa
IIa IIb
IIb
IIb III
III
III
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III
III
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III
III
IIa
IIa
IIa IIb
IIb
IIb III
III
III

Proportional effects of antiplatelet therapy on vascular events (MI,
stroke, or vascular death) in the main high-risk categories.
From Antithrombotic Trialists’ Collaboration: Collaborative meta-analysis of
randomised trials of antiplatelet therapy for prevention of death, myocardial
infarction, and stroke in high-risk patients. BMJ 324:71, 2002

Impact of addition of clopidogrel to aspirin (ASA) in STEMI patients
A, Effects of the addition of clopidogrel in
patients receiving fibrinolysis for STEMI.
Patients in the clopidogrel group (n = 1752)
had a 36% reduction in the odds of dying,
sustaining a recurrent infarction, or having an
occluded infarct artery compared with the
placebo group (n = 1739) in the CLARITY-
TIMI 28 trial
B, Effect of the addition of clopidogrel on
in-hospital mortality after STEMI. These
time-to-event curves show a 0.6%
reduction in mortality in the group
receiving clopidogrel plus aspirin (n =
22,961) compared with placebo plus
aspirin (n = 22,891) in the COMMIT trial.

107
Recommendations for
Use of Parenteral
Anticoagulants in Patients
with STEMI

108
Use of Parenteral Anticoagulants in STEMI
Modified
Recommendati
on
a. For prior treatment with UFH, additional boluses of UFH should be
administered as needed to maintain therapeutic activated clotting time levels,
taking into account whether GP IIb/IIIa receptor antagonists have been
administered
b. Low molecular-weight heparin (LMWH) might be considered an acceptable
alternative to UFH in patients less than 75 years who are receiving fibrinolytic
therapy in the absence of significant renal dysfunction.
c. Bivalirudin is useful as support for primary PCI with or without prior treatment
with heparin.
For patients proceeding to primary PCI, who
have been treated with ASA and a
thienopyridine, recommended supportive
anticoagulant regimens include:
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III
III

UFH vs Enoxaparin
A. The rate of the primary endpoint (death or
nonfatal MI) at 30 days was significantly
lower in the enoxaparin (Enox) group than in
the unfractionated heparin (UFH) group
(9.9% versus 12%; P < 0.001). The dashed
vertical line indicates the comparison at day
2, at which time a trend in favor of
enoxaparin was seen.
B. The rate of the main secondary
endpoint (death, nonfatal MI, or urgent
revascularization) at 30 days was
significantly lower in the Enox group than
in the UFH group (11.7% versus 14.5%; P
< 0.001). The difference was already
significant at 48 hours (6.1% in the UFH
group versus 5.3% in the Emox group; P =
0.02).
Antman EM et al. Enoxaparin versus unfractionated heparin with fibrinolysis for
ST-elevation myocardial Infarction. N Engl J Med 354: 1477, 2006.)

110
HORIZONS-AMI: Design
Stone et al. N Eng J Med. 2008;358:2218-30.
3602 patients with STEMI &
symptom onset ≤ 12 hours
randomized
1800 received bivalirudin alone*
Principal management strategy
Primary PCI, 1678 (93.2%)
Deferred PCI, 5 (0.3%)
CABG, 23 (1.3%)
Medical management, 94 (5.2%)
1802 received heparin +
GP IIb/IIIa inhibitor
Principal Management Strategy
Primary PCI, 1662 (92.2%)
Deferred PCI, 3 (0.2%)
CABG, 40 (2.2%)
Medical Management, 97 (5.4%)
Emergency angiography Emergency angiography
Endpoints: Composite of net adverse clinical events (NACE)
Included major bleeding plus MACE (a composite of CVD death, reinfarction, target-
vessel revascularization for ischemia, and stroke within 30 days)
•

HORIZONS-AMI: RESULTS
• Treatment with bivalirudin was
associated with a significantly
lower rate of major bleeding and
mortality at 30 days
• The cumulative incidence of
major adverse cardiac events
(MACE), which did not differ
between the two strategies at
30 days.
• Acute stent thrombosis during
the first 24 hours was higher in
patients treated with bivalirudin
alone.

Other Pharmacological Measures
Angiotensin converting enzyme (ACE)
inhibitors
Angiotensin receptor blockers (ARB)
Aldosterone blockers
Glucose control
Magnesium
Inhibition of
the renin -
angiotensin -
aldosterone
system

ACE/ARB: Within 24 Hours
An ACE inhibitor should be administered orally
within the first 24 hours of STEMI to the following
patients without hypotension or known class of
contraindications:
• Anterior infarction
 Pulmonary congestion
 LVEF < 0.40
An ARB should be given to ACE-intolerant patients
with either clinical or radiological signs of HF or LVEF
< 0.40.

Effect of angiotensin-converting
enzyme inhibitors on mortality after
myocardial infarction—results from
the long-term trials
Effects of angiotensin-converting
enzyme inhibitors on mortality after
myocardial infarction—results from
the short-term trials.

Effect of a selective aldosterone receptor blocker (eplerenone) after
myocardial infarction
The Kaplan-Meier estimates of the rate of death from cardiovascular
causes or hospitalization for cardiovascular events in the EPHESUS trial
are depicted.
(

116
Intensive Glucose Control in STEMI
NEW
Recommendation
It is reasonable to use an insulin
based regimen to achieve and
maintain glucose levels less than
180 mg/dl while avoiding
hypoglycemia for patients with
STEMI with either a complicated
or
uncomplicated course
I
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III

Arrhythmias During Acute Phase of STEMI:
Electrical Instability
VPBs K+ , Mg++, beta blocker
VT Antiarrhythmics, DC shock
AIVR Observe unless hemodynamic
compromise
NPJT Search for cause (e.g., dig toxicity)
Arrhythmia Treatment

Sinus Tach Treat cause; beta blocker
Afib / Flutter Treat cause; slow ventricular rate; DC shock
PSVT Vagal maneuvers; beta blocker,
verapamil / diltiazem; DC shock
Pump Failure / Excess Sympathetic Tone

Sinus Brady Treat if hemodynamic compromise;
atropine / pacing
Junctional Treat if hemodynamic compromise;
atropine / pacing
Bradyarrhythmias

AV Conduction Disturbances
Escape Rhythm His Bundle Distal
< 120 ms > 120 ms
45 - 60 Often < 30
Duration of AVB 2 - 3 days Transient
Mortality Low High (CHF, VT)
Rx Observe PM (ICD)
Proximal Distal

Recommendations for Treatment of
Atrioventricular and Intraventricular Conduction
Disturbances During STEMI
INTRAVENTRICULAR
CONDUCTION Normal
ACTION CLASS ACTION CLASS ACTION CLASS ACTION CLASS ACTION CLASS ACTION CLASS ACTION CLASS
Observe I Observe I Observe I Observe IIb Observe IIa Observe III Observe III
A III A III A III A* III A III A III A III
TC III TC IIb TC IIb TC I TC I TC I TC I
TV III TV III TV III TV III TV III TV IIa TV IIa
Old or New Observe I Observe IIb Observe IIb Observe IIb Observe IIb Observe III Observe III
Fascicular block A III A III A III A* III A III A III A III
(LAFB or LPFB) TC IIb TC I TC IIa TC I TC I TC I TC I
TV III TV III TV III TV III TV III TV IIa TV IIb
Observe I Observe III Observe III Observe III Observe III Observe III Observe III
TC IIb TC I TC I TC I TC I TC I TC I
TV III TV IIb TV IIb TV IIb TV IIb TV IIa TV IIa
Observe III Observe III Observe III Observe III Observe III Observe III Observe III
TC I TC I TC I TC I TC I TC IIb TC IIb
TV IIb TV IIa TV IIa TV IIa TV IIa TV I TV I
Fascicular Observe III Observe III Observe III Observe III Observe III Observe III Observe III
block + RBBB A III A III A III A* III A III A III A III
TC I TC I TC I TC I TC I TC IIb TC IIb
TV IIb TV IIa TV IIa TV IIa TV IIa TV I TV I
Alternating Observe III Observe III Observe III Observe III Observe III Observe III Observe III
left and right A III A III A III A* III A III A III A III
bundle branch TC IIb TC IIb TC IIb TC IIb TC IIb TC IIb TC IIb
block TV I TV I TV I TV I TV I TV I TV I
Normal
Old bundle
branch block
New bundle
branch block
Mobitz II second degree AV block
Mobitz I second degree AV block
First degree AV block
ANTERIOR MI NON-ANTERIOR ANTERIOR MI NON-ANTERIOR ANTERIOR MI NON-ANTERIOR
Atrioventricular Conduction

Long-Term Management
ACC/AHA Guidelines for the
Management of Patients with
ST-Elevation Myocardial Infarction

Secondary Prevention and Long Term Management
• Assess tobacco use.
• Strongly encourage patient and family to
stop smoking and to avoid secondhand
smoke.
• Provide counseling, pharmacological
therapy (including nicotine replacement and
bupropion), and formal smoking cessation
programs as appropriate.
Smoking
Goal:
Complete
Cessation
Goals Recommendations

If blood pressure is 120/80 mm Hg or greater:
• Initiate lifestyle modification (weight control, physical
activity, alcohol moderation, moderate sodium restriction, and
emphasis on fruits, vegetables, and low-fat dairy products) in
all patients.
If blood pressure is 140/90 mm Hg or greater or 130/80
mm Hg or greater for individuals with chronic kidney
disease or diabetes:
• Add blood pressure-reducing medications, emphasizing the
use of beta-blockers and inhibitors of the renin-angiotensin-
aldosterone system.
Blood pressure
control:
Goal: < 140/90
mm Hg or
<130/80 mm Hg
if chronic kidney
disease or
diabetes

• Assess risk, preferably with exercise test, to guide
prescription.
• Encourage minimum of 30 to 60 minutes of activity,
preferably daily but at least 3 or 4 times weekly (walking,
jogging, cycling, or other aerobic activity) supplemented by
an increase in daily lifestyle activities (e.g., walking breaks
at work, gardening, household work).
• Cardiac rehabilitation programs are recommended for
patients with STEMI.
Physical activity:
Minimum goal:
30 minutes 3 to 4
days per week;
Optimal daily

• Start dietary therapy in all patients (< 7% of total calories as
saturated fat and < 200 mg/d cholesterol). Promote physical
activity and weight management. Encourage increased
consumption of omega-3 fatty acids.
• Assess fasting lipid profile in all patients, preferably within
24 hours of STEMI. Add drug therapy according to the
following guide:
Lipid
management:
(TG less than
200 mg/dL)
Primary goal:
LDL-C << than
100 mg/dL
LDL-C < 100 mg/dL (baseline or on treatment):
Statins should be used to lower LDL-C.
LDL-C ≥ 100 mg/dL (baseline or on
treatment):
Intensify LDL-C–lowering therapy with drug treatment,
giving preference to statins.

If TGs are ≥ 150 mg/dL or HDL-C is < 40 mg/dL:
Emphasize weight management and physical
activity. Advise smoking cessation.
If TG is 200 to 499 mg/dL:
After LDL-C–lowering therapy, consider adding
fibrate or niacin.
If TG is ≥ 500 mg/dL:
Consider fibrate or niacin before LDL-C–lowering
therapy.
Consider omega-3 fatty acids as adjunct for high
TG.
Lipid
management:
(TG 200 mg/dL
or greater)
Primary goal:
Non–HDL-C <<
130 mg/dL

Calculate BMI and measure waist circumference
as part of evaluation. Monitor response of BMI
and waist circumference to therapy.
Start weight management and physical activity as
appropriate. Desirable BMI range is 18.5 to 24.9
kg/m2.
If waist circumference is ≥ 35 inches in women or
≥ 40 inches in men, initiate lifestyle changes and
treatment strategies for metabolic syndrome.
Weight
management:
Goal:
BMI 18.5 to 24.9
kg/m2
Waist
circumference:
Women: < 35 in.
Men: < 40 in.

Appropriate hypoglycemic therapy to
achieve near-normal fasting plasma
glucose, as indicated by HbA1c.
Treatment of other risk factors (e.g.,
physical activity, weight management,
blood pressure, and cholesterol
management).
Diabetes
management:
Goal:
HbA1c < 7%

• In the absence of contraindications, start aspirin
75 to 162 mg/d and continue indefinitely.
• If aspirin is contraindicated, consider clopidogrel
75 mg/day or warfarin.
• Manage warfarin to INR 2.5 to 3.5 in post-
STEMI patients when clinically indicated or for
those not able to take aspirin or clopidogrel.
Antiplatelet
agents/
anticoagulants

ACE inhibitors in all patients indefinitely; start early in
stable, high-risk patients (ant. MI, previous MI, Killip class
≥ 2 [S3 gallop, rales, radiographic CHF], LVEF < 0.40).
Angiotensin receptor blockers in patients who are
intolerant of ACE inhibitors and with either clinical or
radiological signs of heart failure or LVEF < 0.40.
Aldosterone blockade in patients without significant renal
dysfunction or hyperkalemia who are already receiving
therapeutic doses of an ACE inhibitor, have LVEF ≤ 0.40,
and have either diabetes or heart failure.
Renin-
Angiotensin-
Aldosterone
System
Blockers

Start in all patients. Continue indefinitely.
Observe usual contraindications.
Beta-
Blockers

• Meta-analysis of effects of intravenous and then oral beta blocker therapy on
death, reinfarction, and cardiac arrest during the scheduled treatment periods in
26 small randomized trials, MIAMI, ISIS-1, and the low-risk subset of COMMIT.

Cardiac Rehabilitation
Cardiac rehabilitation/secondary prevention
programs, when available, are recommended
for patients with STEMI, particularly those
with multiple modifiable risk factors and/or
those moderate- to high-risk patients in whom
supervised exercise training is warranted.

FUTURE PERSPECTIVES
Multiple mechanisms involved in the pathogenesis of no-reflow that might be
targeted by appropriate therapy.

The demonstration that some cardiomyocytes are regenerated after birth
highlights the promise and challenges of future regenerative cardiac
therapies. Autologous and allogeneic sources of cells that may give rise to
cardiomyocytes are under investigation

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